Optimizing the utilization of aluminum adjuvants in vaccines: you might just get what you want

Abstract

Aluminum-containing adjuvants have been used for over 90 years to enhance the immune response to vaccines. Recent work has significantly advanced our understanding of the physical, chemical, and biological properties of these adjuvants, offering key insights on underlying mechanisms. Given the long-term success of aluminum adjuvants, we believe that they should continue to represent the "gold standard" against which all new adjuvants should be compared. New vaccine candidates that require adjuvants to induce a protective immune responses should first be evaluated with aluminum adjuvants before other more experimental approaches are considered, since use of established adjuvants would facilitate both clinical development and the regulatory pathway. However, the continued use of aluminum adjuvants requires an appreciation of their complexities, in combination with access to the necessary expertise to optimize vaccine formulations. In this article, we will review the properties of aluminum adjuvants and highlight those elements that are critical to optimize vaccine performance. We will discuss how other components (excipients, TLR ligands, etc.) can affect the interaction between adjuvants and antigens, and impact the potency of vaccines. This review provides a resource and guide, which will ultimately contribute to the successful development of newer, more effective and safer vaccines.

Fig. 1

Formulation of an effective vaccine with aluminum adjuvants requires knowledge of the chemical and physical properties of the adjuvant and rigorous characterization of the antigen and antigen−adjuvant formulation. Excipients can affect the antigen−adjuvant interactions

Fig. 2

Structure of aluminum hydroxide adjuvant (a) and aluminum phosphate adjuvant (b). Images were obtained by cryo-electron microscopy. Scale bar = 200 nm